CN107106820A - Treat the chemical ablation and method of a variety of diseases - Google Patents

Abstract

Embodiment of the present invention by the formulation delivered of effective dose to tissue by providing the apparatus and method for being used for treating at least one：Hypertension, pulmonary artery, diabetes, obesity, heart failure, ESRD, DD, urological disorders, cancer, tumour, pain, asthma or chronic obstructive pulmonary disease.In embodiments of the invention, the preparation may include at least one gas, steam, liquid, solution, emulsion or suspension of one or more compositions.In embodiments of the invention, the effectively damage of the amount of the preparation and/or energy or destruction tissue, nerve and nerve endings and then alleviation disease symptomses.

Description

Treat the chemical ablation and method of a variety of diseases

The U.S. Provisional Patent Application No. 62/122,818 submitted this application claims on October 30th, 2014 and in January, 2015 The priority for the U.S. Provisional Patent Application No. 62/124,868 submitted for 5th, its each content is incorporated herein by by carrying stating.

Embodiment of the present invention is related to treatment hypertension, pulmonary hypertension, diabetes, obesity, eventually heart failure, end Phase nephrosis, DD, cancer, tumour, pain, chemical infusion device, the system of asthma or chronic obstructive pulmonary disease (COPD) Agent and method.Described device may include air bag and the combination of infusion catheter and other delivery apparatus.The preparation can include one Gas, steam, liquid, solution, emulsion and the suspension of kind or Multiple components.Methods described is related to will be described by chemistry infusion Target tissue of the formulation delivered into human body.

Hypertension (Hypertension) or hypertension (high blood pressure) are global Major health problems. The Adult group for being estimated to be 30-40% in the world suffers from the patient's condition.Additionally, it is contemplated that its popularity degree will increased, particularly In developing country.The diagnosis and treatment of hypertension are still suboptimum, and patient is difficult to rationally control blood pressure mostly.

Benign prostate hyperplasia is the non-cancerous increase of prostate, and it influences the age more than 50% percentage more than 60 The male in year.Early stage life, prostate is about walnut size, weighs about 20 grams.Over time, prostatitis hylperadenosis It is considered as normal.With advancing age, prostate is gradually increased at least twice of its original size.Prostatic growth To neighbouring urethra build-up of pressure, cause latter organ to narrow, and ultimately result in ureteral obstruction, make dysuria.

Chronic obstructive pulmonary disease (COPD) is related to two kinds of main airflow obstruction illnesss：Chronic bronchitis and lung qi It is swollen.Chronic bronchitis is as caused by bronchial airways inflammation.Tracheae is connected by bronchial airways with lung.Pulmonary emphysema are a kind of Excessively expanded by alveolar or lung's air bag caused by disease.The patient's condition causes short of breath.16,000,000 Americans are there are about to suffer from COPD, wherein most of (80-90%) are lifelong smokers.COPD is the major causes of death in the U.S..

Asthma is a kind of chronic respiratory disease, it is characterised in that air flue excessively narrows, and by airway inflammation, unnecessary mucus Generation and airway hyperreactivity cause.The air flue narrows and makes expiratory dyspnea, it is possible to significantly affect the life of patient, limitation ginseng With numerous activities.In severe cases, asthma attack may threat to life.So far, without known healing asthma Method.

Chronic nasosinusitis (CS) is caused by film liner (membrane lining) inflammation in one or more paranasal sinus , and it is generally relevant with significant tissue damage.The annual CS about 37,000,000 reported to CDC (CDC) Example.

Diabetes are a kind of metabolism patient's condition, or the patient's condition combination, wherein Individual Experience high blood glucose concentration.The patient's condition is by body Interior insulin generation deficiency or cell can not be responded suitably caused by insulin.Glycosylated hemoglobin (HbA1c) is used as blood plasma Portugal The label of grape sugar concentration plays a role, and is clinically used to diagnose diabetes.In people, normal HbA1c levels are usual< 6.0%, the HbA1c horizontal extents of prediabetes (prediabetes) are 6.0-6.4%, and the HbA1c levels of diabetes are super Cross 6.5%.

In the U.S. and other developed countries, diabetes are dead and disabled one of the main reasons.It is several with influence body The long-term complications of each section are related.For example, it and blindness, heart and vascular diseases, apoplexy, kidney failure, amputation and god It is relevant through damaging.

In the U.S., diabetes have impact on about 8% population, and cause the expense close to 250,000,000,000 dollars.

Diabetes are generally divided into 1 type (also referred to as insulin-dependent diabetes mellitus or adolescent diabetes), 2 types (also referred to as Non-Insulin Dependent Diabetes Mellitus, Adult Onset's patients with type Ⅰ DM or fat related diabetes) or gestational diabetes mellitus, wherein 1 type Patient can not produce enough insulin, and 2 type patients can not be to the appropriate response of insulin, and gestational diabetes mellitus is in pregnant female evening The patient's condition that phase develops.

Diabetes B is the most common form of diabetes, accounts for the 90-95% of overall case.Its generally with it is old, fat, Family history, glycosuria gravidarum medical history before are related to sluggish body movement.It is also more universal in some races.2 types Diabetes are also referred to as insuline resistant diabetes, because pancreas generally produces the insulin of sufficient amount, but body can not suitably ring It answer it.The symptom related to diabetes B includes fatigue, frequent micturition, increased thirsty and hungry, weight loss, eyesight mould Paste and wound or sore indolence.

Obesity is another Major health problems, particularly in developed country.It is a kind of complicated, multifactor and chronic disease Condition, it is characterised in that excessive body fat, this is caused by the imbalance between energy expenditure and calorie intake.Although this Unbalanced reason is planted not yet completely to understand, but hereditary and/or acquired physiological event and environmental factor are considered as to contribute 's.The adverse health influence relevant with obesity and particularly morbid obesity is more conclusive in recent years.This adverse reaction bag Include but be not limited to angiocardiopathy, diabetes, hypertension, arthritis and sleep apnea.In general, referring to weight in patients Number (BMI) rise, suffers from and is also raised to the possibility of fat related ill-effect.

The present invention is provided to treat hypertension, diabetes, obesity, heart failure, ESRD, digestive system disease Disease, disease in the urological system, cancer, tumour, pain, the new apparatus and method of asthma and chronic obstructive pulmonary disease (COPD).Institute State new method and be related to chemical infusion and delivery system and strategy.This method focuses on the illness into human body by formulation delivered Organize and the security and effect for the treatment of can be improved.

Embodiment of the present invention be related to by by the formulation delivered of effective dose to illing tissue carry out for hypertension, Diabetes, obesity, heart failure, ESRD, disease of digestive system, cancer, tumour, pain, asthma and chronic obstructive The treatment of lung disease (COPD).This preparation includes gas, steam, liquid, solution, emulsion and the suspension of one or more compositions Liquid.Method is related to the luminal surface and tissue in preparation controllable delivery to human body so that those regions are modified.These sides Method can cause the denervation of nerve and nerve endings in body cavity.Methods described may also include the favourable of neural and nerve endings Cut off and then interrupt nerve exchange.Temperature can strengthen the security and effect for the treatment of preparation.The scope of temperature can be -40 to 140 DEG C, -30 to 100 DEG C or -30 to 80 DEG C.In some embodiments, preparation includes the one of binary, ternary or four-tuple point, And more than four kinds components can be included.Delivering method includes invasive less transcutaneous modalities and non-invasive manner.The present invention's Embodiment provides preparation and delivery catheter, and it strengthens the absorption for entering body tissue and tube chamber nerve and nerve endings and worn Thoroughly.

In one embodiment, at least one composition of preparation is selected from：Water, salt solution, hypertonic saline, phenols, methanol, second Alcohol, absolute alcohol, isopropanol, propyl alcohol, butanol, isobutanol, ethylene glycol, glycerine, acetic acid, lactic acid, propyl iodide, isopropyl iodide, second Base iodine, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, lipiodol, surfactant, and its Derivative and combination.

In one embodiment, at least one formulation ingredients are gas.The gas includes one of the following：Oxygen, nitrogen Gas, helium, argon gas, air, carbon dioxide, nitric oxide, organic and inorganic compound steaming gas and water, phenol, methanol, ethanol, Absolute alcohol, isopropanol, propyl alcohol, butanol, isobutanol, ethylene glycol, glycerine, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl Iodine, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, and its derivative and combination.

In one embodiment, at least one composition of preparation is surfactant.The surfactant includes PEG Laurate, polysorbas20, polysorbate40, polysorbate60, Tween 80, PEG oleates, PEG stearates, PEG glyceryl laurate esters, It is PEG glyceryl oleates, PEG stearines, polyglyceryl laurate, Unigly GO 102S, polyglyceryl myristate, poly- Palmitin, the laurate of polyglycereol -6, the oleate of polyglycereol -6, the myristinate of polyglycereol -6, the palm of polyglycereol -6 Acid esters, Natrulon H-10 laurate, Natrulon H-10 oleate, Natrulon H-10 myristinate, Natrulon H-10 palmitate, PEG Arlacel-20s, PEG Arlacel-20s, PEG Arlacel-80s, PEG dehydrations Sorbitan stearate, PEG oleyl ethers, PEG bays ether, organic acid, any organic acid and organic amine salt, bunching water it is sweet Oil, glycerine, poly-glycerine, galactitol, two (ethylene glycol), three (ethylene glycol), four (ethylene glycol), five (ethylene glycol), poly- (second two Alcohol) oligomer, two (propane diols), three (propane diols), four (propane diols), five (propane diols), poly- (propane diols) oligomer, poly- second two The block copolymer of alcohol and polypropylene glycol, Pluronic, Pluronic 85 and its derivative and combination.

In one embodiment, preparation at least includes oil, aliphatic acid and/or lipid.In some embodiments, preparation In oil at least, aliphatic acid and/or lipid be selected from butyric acid (butanoic acid), caproic acid (hexanoic acid), octanoic acid (octanoic acid), capric acid (decanoic acid), dodecylic acid, tetradecanoic acid, hexadecanoic acid, octadecanoid acid, 18 Carbon trienic acid, arachic acid, eicosenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, fertility three Alkene phenol, butyric acid (butyric acid), caproic acid (caproic acid), sad (caprylic acid), capric acid (lauric Acid), laurate, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, isonicotinic acid, linoleic acid, alpha-linolenic acid, γ- Leukotrienes, behenic acids, erucic acid, tetracosa carbon are sour, natural or synthetic phosphatide, single-, two- or triacylglycerol, cuorin, phosphatide Acyl glycerine, phosphatidic acid, phosphatidyl choline, alpha-tocopherol, phosphatidyl-ethanolamine, sphingomyelins, phosphatidylserine, phosphatidyl-4 Alcohol, dimyristoyl phosphatidyl choline, DOPC, DPPC, distearoylphosphatidyl courage Alkali, phosphatidyl-ethanolamine, phosphatidyl glycerol, sphingolipid, prostaglandin, gangliosides, NEOBEE, vesicle (niosome) and its Derivative.

In another embodiment, preparation includes the therapeutic agent or medicine of the denervation for nerve.The treatment Agent includes one of the following：Sodium channel blockers, tetraodotoxin (tetrodotoxin), shellfish poison (saxitoxin), deaminizating Formyl shellfish poison, Vanillin (vanilloid), N-STX (neosaxitoxin), lidocaine, conotoxin (conotoxin), cardiac glycoside (cardiac glycoside), digoxin, glutamic acid, staurosporin (staurosporine), Amlodipine (amlodipine), Verapamil (verapamil), cymarin (cymarin), ocean ground Pornography and drug glycosides (digitoxin), Proscillaridin (proscillaridin), quabain, veratridine (veratridine), cartilage algae Sour (domoic acid), ethanol, oleandrin (oleandrin), carbamazepine (carbamazepine), aflatoxin (aflatoxin), guanethidine (guanethidine) and guanethidine monosulphate.In another embodiment, the preparation includes using In the contrast agent of the denervation imaging to nerve.Such contrast agent includes one of the following：Iodine, ethyl iodide, sodium iodide, iodine Oil, nonoxinol iodine, iobitridol, Iohexol, iomeprol, Iopamidol, Iopentol, Iopromide, Ioversol, Ioxilan, iodine are bent Logical sequence, Iodixanol or Ioxaglic Acid and its derivative.

In one embodiment, the preparation includes azeotropic mixture.Azeotropic mixture is can not be changed by simple distillation two The mixture of kind or Multiple components.The steam produced when it is due to boiling has the group proportional to original stock Point.Potential preparation azeotropic mixture includes ethanol/water, ethanol/water/contrast agent, ethanol/water/surfactant, ethanol/water/radiography Agent/surfactant, propanol/water, isopropanol/water, butanol/water, acetic acid/water and combinations thereof.

In one embodiment, preparation is in gas or vapor state and includes one or more compositions.Steam or gas Preparation may include one of the following：Oxygen, nitrogen, helium, argon gas, air, carbon dioxide, nitric oxide, water, phenol, methanol, second Alcohol, absolute alcohol, isopropanol, propyl alcohol, butanol, isobutanol, ethylene glycol, glycerine, acetic acid, lactic acid, propyl iodide, isopropyl iodide, second Base iodine, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate and its mixture.In an embodiment In, steam preparation includes one that following binary, ternary or four-tuple are divided, and can include more than four kinds components.Steam preparation can be wrapped Azeotropic mixture or contrast agent, such as lipiodol or iodine are included, and may include surfactant and/or therapeutic agent.The elevated temperature of steam preparation Scope can be 0 DEG C to 140 DEG C, 15 DEG C to 100 DEG C or 20 DEG C to 85 DEG C.

In one embodiment, the preparation is in a liquid state and including one or more compositions.Under liquid preparation may include One of state：Water, salt solution, hypertonic saline, phenol, methanol, ethanol, absolute alcohol, isopropanol, propyl alcohol, butanol, isobutanol, second two Alcohol, glycerine, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, lipiodol, methyl acetate, ethyl acetate, ethyl nitrate, acetic acid Isopropyl ester, ethyl lactate, urea, surfactant and other.Liquid preparation may include azeotropic mixture, contrast agent and/or therapeutic agent. In one embodiment, preparation may include the one of binary, ternary or four-tuple point, and may also include more than four kinds components. In some embodiments, the temperature range of liquid preparation can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 ℃.Liquid preparation may include solution, suspension and emulsion.

In one embodiment, include for treating the method for disease by delivery catheter is percutaneous and/or oral insert people Illing tissue in body；Using the conduit so that the tissue that preparation infusion enters the body of people will be treated, wherein what is delivered is described The amount of preparation can for example by reduce blood pressure, reduce G/W it is gentle mitigate it is short of breath it is effective damage or destruction as described in group Knit；Optionally remove the preparation；Finally delivery catheter is recalled from body.The disease of the medical needle pair includes one of the following：It is high Blood pressure, pulmonary hypertension, diabetes, obesity, heart failure, ESRD, DD, cancer, tumour, pain, Asthma or chronic obstructive pulmonary disease (COPD).Suitable for the treatment body cavity include the arteria renalis and vein, pulmonary artery, lumen of vessels, Arteria coeliaca, common and appropriate arteria hepatica, gastroduodenal artery, left and right arteria hepatica, arteria linenalis, left and right arteria gastrica, non-blood Tube chamber, air flue, sinus, oesophagus, respiratory cavity, gastrovascular cavity, Stomach duodenum, jejunum, cancer, tumour, pain and uropoiesis chamber.It is suitable Include oesophagus, Stomach duodenum, jejunum, small intestine and large intestine and colon in the gastrovascular cavity of the treatment.Preparation bag suitable for the treatment Include gas, steam, liquid, solution, emulsion and the suspension of one or more compositions.If the preparation includes one or more The steam of composition, can generate heat by the way that steam condensation is turned into liquid in the tissue.If preparation includes liquid or solution, cooling Heat can from be less than or more than body temperature formulation temperature generate.The scope of liquid preparation temperature can be -40 DEG C to 140 DEG C, -30 DEG C To 100 DEG C or -20 DEG C to 80 DEG C.In one embodiment, formulation temperature can be equal to room temperature.In one embodiment, make The scope of agent temperature can be -40 DEG C to -20 DEG C.In another embodiment, the scope of formulation temperature can be 15 DEG C to 80 DEG C. In one embodiment, formulation temperature can be equal to body temperature.In another embodiment, the scope of formulation temperature can be 50 DEG C to 80 ℃.In another embodiment, the temperature of the tissue through treatment can be less than formulation temperature and higher than body temperature.Tissue through treatment The scope of temperature can be -40 DEG C to 100 DEG C, -30 DEG C to 80 DEG C or -20 DEG C to 80 DEG C.In one embodiment, through treatment The scope of the temperature of tissue can be -40 DEG C to -20 DEG C.In another embodiment, the scope of the temperature of the tissue through treatment can For 15 DEG C to 80 DEG C.In one embodiment, the temperature of the tissue through treatment can be equal to body temperature.In another embodiment, The scope of the temperature of tissue through treatment can be 50 to 80 DEG C.Delivery catheter suitable for this treatment includes the pin under imaging is oriented to Or the conduit based on pin.Imaging, which is oriented to, includes one of ultrasound, X-ray, CT scan, MRI, OCT or viewer (scope).Delivering Conduit can also be based on air bag.This conduit based on air bag can have single, double or three air bags.Delivery catheter can also be Based on infusion.The combination of air bag and infusion catheter can also be used in operation.In one embodiment, methods described includes Rinse and moved with protecting and diluting from catheter distal tip line-transect tube chamber (catheter distal tip like wire lumen) The chemicals of shifting, and prevent chemicals out of control from entering the distal portions of non-area for treatment；Rinsed from infusion catheter；From endoscope Rinse；Preparation is removed or recall from body tissue and tube chamber and use normal saline washing target region after the treatment after treatment.

It is understood that foregoing general description and detailed description below are exemplary and merely for explanation mesh , and be not intended to limit such as claimed content.

Brief description

Fig. 1 is the exemplary of the perspective view of the double bolloon delivery catheter according to the present invention.

Fig. 2 is the embodiment of the side view of the distal portions of the dumbbell air bag of expansion.

Fig. 3 A are the embodiments of the side view on airbag wall with the infusion air bag for being used for the hole that chemical agent is delivered.

Fig. 3 B are the embodiments of the side view for the chemical agent delivery systems being positioned in the body cavity with swelling gasbag, are changed Agent is learned to be mainly limited between two expanded diameter sections.

Fig. 4 A are the embodiments of the side view of the infusion device with the chemical agent delivery tube being attached with air bag.

Fig. 4 B are the realities with the side view of the dumbbell air bag infusion device of the tapering transition of diameter from larger to less Apply scheme, and the chemical agent delivery tube being attached.

Fig. 5 A are to prove that preparation is transfused to the embodiment for entering air flue using monosaccate delivery catheter.

Fig. 5 B are to prove that preparation is transfused to the embodiment for entering air flue using double bolloon delivery catheter.

Fig. 5 C are to prove that preparation is transfused to the embodiment for entering the arteria renalis using double bolloon delivery catheter.

Fig. 6 is the embodiment of the fragmentary cross-sectional views of double bolloon delivery catheter in body cavity.

Fig. 7 is the implementation of the fragmentary cross-sectional views of three air bags on the multi-lumen shaft with expansion chamber and agent delivery lumen Scheme.

Fig. 8 A are that the three air bags combination with reduced un-occupied space is defeated between two larger diameter air bags in swelling state The embodiment of the fragmentary cross-sectional views of dispensing device.

Fig. 8 B are the offices of the three air bag infusion devices with the different air bag waist orientations for attachment of the air bag on axle The embodiment of portion's cross-sectional view strength.

Fig. 9 A are the realities of the fragmentary cross-sectional views of the double bolloon infusion device of the expansion with infusion port between air bag Apply scheme.

Fig. 9 B are the double bolloons with tapered diameter change and the expansion of the small diameter in the center section of double bolloon The embodiment of the fragmentary cross-sectional views of infusion device.

Fig. 9 C be with combination two benches air bag and the small diameter in the center section of double bolloon component can be swollen The embodiment of the fragmentary cross-sectional views of swollen double bolloon infusion device.

Figure 10 A are the embodiments that preparation is infused to left arteria gastrica using monosaccate delivery catheter.

Figure 10 B are that preparation is infused into hepatic arterial embodiment using monosaccate delivery catheter.

Figure 11 is that preparation is infused into duodenal embodiment using three air bag delivery catheters.

Figure 12 is to prove that norepinephrine (NE) is reduced after kidney denervation in ethanol-vs. randomized controlled treatment groups Bar chart.

Figure 13 is to prove the curve using weight change after second acid treating agent duodenum.

Figure 14 is to prove the curve using weight change after ethanol agent treatment duodenum.

Figure 15 is the embodiment of the metal infusion tube with Ahmedabad triangle features (Bard triangle feature) (as shown in by white arrow).

Figure 16 is the histopathology image for proving to cut off renal nerve after ethanol treatment (as shown in by black arrow).

Explanation

Embodiment of the present invention is by the way that target tissue of the formulation delivered of effective dose into body cavity to be directed to the treatment of disease. The disease can be one of the following：Hypertension, pulmonary hypertension, diabetes, obesity, heart failure, ESRD, disappear The property changed disease, cancer, tumour, pain, asthma or chronic obstructive pulmonary disease (COPD).Cancer includes adrenal gland, bladder, uterus Neck, colon, oesophagus, gall-bladder, kidney, liver, lung, ovary, pancreas, prostate, rectum, stomach and the cancer in uterus.Preparation includes one kind Or gas, steam, liquid, solution, emulsion and the suspension of Multiple components.Methods described is related to formulation delivered into human body Luminal surface, tissue and nerve so modify these surfaces, tissue and nerve.The body cavity includes the arteria renalis and vein, lung are dynamic Arteries and veins, lumen of vessels, arteria coeliaca, arteria hepatica communis, proper hepatic artery, gastroduodenal artery, right hepatic artery, left hepatic artery, spleen are moved Arteries and veins, right arteria gastrica, left arteria gastrica, blood vessel, non-vascular chamber, air flue, sinus, oesophagus, respiratory cavity, gastrovascular cavity, Stomach duodenum, Jejunum, cancerous tissue, tumour and uropoiesis chamber.Gastrovascular cavity includes oesophagus, Stomach duodenum, jejunum, small intestine and large intestine and colon.Temperature Degree can strengthen the security and effect for the treatment of preparation.Temperature range can be for -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C extremely 80℃.The temperature of tissue through treatment can be differently configured from formulation temperature.The temperature range of tissue through treatment can be for -40 DEG C extremely 100 DEG C or -30 DEG C to 80 DEG C.Illing tissue can effectively be damaged, destroy or be eliminated to the preparation of delivering and the amount of energy, such as example By reducing blood pressure, reducing tumour, pain of alleviation or alleviate asthma or COPD symptom.Energy or heat can by accelerate preparation and Reaction rate enhancing damage/destruction/elimination effect between tissue.The method of delivering includes formulation delivered surrounding human body to melt The nerve of chamber.This method includes removing or recall preparation from tissue or tube chamber after the treatment.

In one embodiment, preparation is the one of single chemical agent or binary, ternary or four-tuple point, and be may also include many In four kinds of component.In one embodiment, delivery system may include aggressive less transcutaneous modalities or Non-Invasive side Formula.Embodiment of the present invention includes the surface modification containing one or more enhancing body cavitys and enters the tissue and nerve of body cavity The preparation of absorption and the composition penetrated with nerve endings.

In one embodiment, the composition of preparation is selected from：It is water, salt solution, hypertonic saline, phenol, methanol, ethanol, anhydrous Alcohol, isopropanol, propyl alcohol, butanol, isobutanol, ethylene glycol, glycerine, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, second Sour methyl esters, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, lipiodol, surfactant and its derivative and Combination.

In one embodiment, the composition of preparation includes gas.Gas may be selected from：Oxygen, nitrogen, helium, argon gas, sky Gas, carbon dioxide, nitric oxide, organic and inorganic compound steaming gas and water, phenol, methanol, ethanol, absolute alcohol, isopropyl Alcohol, propyl alcohol, butanol, isobutanol, ethylene glycol, glycerine, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, second Acetoacetic ester, ethyl nitrate, isopropyl acetate, ethyl lactate and its mixture.

In one embodiment, the composition in preparation includes surfactant.In some embodiments, surface-active Agent is selected from：PEG laurates, polysorbas20, polysorbate40, polysorbate60, Tween 80, PEG oleates, PEG stearates, PEG bays Acid glyceride, PEG glyceryl oleates, PEG stearines, polyglyceryl laurate, Unigly GO 102S, polyglycereol Pork and beans It is cool acid esters, POGE-A, the laurate of polyglycereol -6, the oleate of polyglycereol -6, the myristinate of polyglycereol -6, poly- sweet Oily -6 palmitates, Natrulon H-10 laurate, Natrulon H-10 oleate, Natrulon H-10 myristinate, Natrulon H-10 Palmitate, PEG Arlacel-20s, PEG Arlacel-20s, PEG anhydro sorbitol list oleic acid Ester, PEG sorbitan stearates, PEG oleyl ethers, PEG bays ether, organic acid, the salt of any organic acid and organic amine, Poly epihydric alcohol, glycerine, poly-glycerine, galactitol, two (ethylene glycol), three (ethylene glycol), four (ethylene glycol), five (ethylene glycol), PEG oligomer, two (propane diols), three (propane diols), four (propane diols), five (propane diols), poly- (propane diols) are oligomeric Thing, the block copolymer of polyethylene glycol and polypropylene glycol, Pluronic, Pluronic 85 and its derivative and combination.At some In embodiment, the scope of the content of surfactant can be 0.1%- by weight by weight 80%, by weight in preparation 0.5%- by weight 50% or 1%- by weight by weight 15%.

In one embodiment, preparation includes at least one of oil, aliphatic acid and/or lipid.Oil, fat in preparation At least one of acid and lipid is selected from：Butyric acid (butanoic acid), caproic acid (hexanoic acid), octanoic acid (octanoic Acid), capric acid (decanoic acid), dodecylic acid, tetradecanoic acid, hexadecanoic acid, octadecanoid acid, octatecatrienoic acid, two Ten alkanoic acids, eicosenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, tocotrienols, butyric acid (butyric acid), caproic acid (caproic acid), sad (caprylic acid), capric acid (lauric acid), bay Acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, isonicotinic acid, linoleic acid, alpha-linolenic acid, gamma-Linolenic acid, Shan Yu Acid, erucic acid, tetracosa carbon are sour, natural or synthetic phosphatide, single-, two- or triacylglycerol, cuorin, phosphatidyl glycerol, phosphatide Acid, phosphatidyl choline, alpha-tocopherol, phosphatidyl-ethanolamine, sphingomyelins, phosphatidylserine, phosphatidylinositols, two myristoyls Phosphatidyl choline, DOPC, DPPC, DSPC, phosphatidyl ethanol Amine, phosphatidyl glycerol, sphingolipid, prostaglandin, gangliosides, NEOBEE, vesicle (niosome) and its derivative.

In another embodiment, preparation includes the therapeutic agent or medicine of the denervation and surface modification for nerve Thing.Therapeutic agent is one of the following：Sodium channel blockers, tetraodotoxin (tetrodotoxin), shellfish poison (saxitoxin), Deaminizating formyl shellfish poison, Vanillin (vanilloid), N-STX (neosaxitoxin), lidocaine, cone shell Toxin (conotoxin), cardiac glycoside (cardiac glycoside), digoxin, glutamic acid, staurosporin (staurosporine), Amlodipine (amiodipine), Verapamil (verapamil), cymarin (cymarin), ocean ground Pornography and drug glycosides (digitoxin), Proscillaridin (proscillaridin), quabain, veratridine (veratridine), cartilage algae Sour (domoic acid), ethanol, oleandrin (oleandrin), carbamazepine (carbamazepine), aflatoxin (aflatoxin), guanethidine (guanethidine) and guanethidine monosulphate.In another embodiment, preparation include be used for pair The contrast agent of the denervation imaging of nerve.This contrast agent include iodine, ethyl iodide, sodium iodide, lipiodol, nonoxinol iodine, Iobitridol, Iohexol, iomeprol, Iopamidol, Iopentol, Iopromide, Ioversol, Ioxilan, Iotrolan, Iodixanol, iodine Gram acid and its derivative.The content range of contrast agent can be 2-25% by weight in preparation, or be 5-15% by weight.

In one embodiment, the preparation includes azeotropic mixture.Azeotropic mixture is can not be changed by simple distillation two The mixture of kind or Multiple components.The steam produced when it is due to boiling has the group proportional to original stock Point.Azeotropic mixture is selected from ethanol/water, ethanol/water/contrast agent, ethanol/water/surfactant, ethanol/water/contrast agent/surface and lived Property agent, propanol/water, isopropanol/water, butanol/water and acetic acid/water.

In one embodiment, preparation is in gas or vapor state, including one or more compositions.In an embodiment party In case, gas or steam preparation include one of the following：Oxygen, nitrogen, helium, argon gas, air, carbon dioxide, nitric oxide and The steam of organic and inorganic compound.The steam of organic and inorganic compound includes one of the following：Water, phenol, methanol, ethanol, Absolute alcohol, isopropanol, propyl alcohol, butanol, isobutanol, ethylene glycol, glycerine, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl Iodine, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate and its mixture.

In one embodiment, the steam preparation includes at least one contrast agent, such as lipiodol or iodine, or azeotropic mixture, And can also include surfactant and/or therapeutic agent.In one embodiment, steam is that binary, ternary or four-tuple divide it One, and may also include more than four kinds components.The temperature range of steam preparation can be 0 DEG C to 140 DEG C, 15 DEG C to 100 DEG C or 30 DEG C To 80 DEG C.

In one embodiment, preparation is in a liquid state, including one or more compositions.Liquid preparation includes one of the following： Water, salt solution, hypertonic saline, phenols, methanol, ethanol, absolute alcohol, isopropanol, propyl alcohol, butanol, isobutanol, ethylene glycol, glycerine, Acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, lipiodol, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, Ethyl lactate, urea, surfactant etc..In one embodiment, the liquid preparation includes contrast agent and/or azeotropic Thing, and can also include therapeutic agent.In one embodiment, liquid preparation is the one of binary, ternary or four-tuple point, and may be used also Include more than four kinds components.In one embodiment, liquid preparation includes solution, emulsion or suspension.The temperature of liquid preparation It can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -30 DEG C to 80 DEG C to spend scope.In one embodiment, formulation temperature can To be room temperature.In one embodiment, the scope of formulation temperature can be -40 DEG C to -20 DEG C.In another embodiment, make The scope of agent temperature can be 15C-80 DEG C.In one embodiment, formulation temperature can be equal to body temperature.In another embodiment In, formulation temperature scope can be 50 DEG C to 80 DEG C.

In one embodiment, include for treating the method for disease by delivery catheter is percutaneous or oral insert body； Using the conduit so that preparation to be infused to illing tissue or the tube chamber in body；Optionally removed from the illing tissue or body cavity Or recall the preparation；Finally delivery catheter is recalled from the body.The disease for the treatment of include hypertension, pulmonary hypertension, Diabetes, obesity, heart failure, ESRD, DD, urologic disease, cancer, tumour, pain, asthma and Chronic obstructive pulmonary disease (COPD).Cancer include adrenal gland, bladder, cervix, colon, oesophagus, gall-bladder, kidney, liver, lung, ovary, Pancreas, prostate, rectum, stomach and the cancer in uterus.Body cavity includes the arteria renalis, lumen of vessels, arteria coeliaca, arteria hepatica communis and intrinsic Artery, gastroduodenal artery, right and left arteria hepatica, arteria linenalis, right and left arteria gastrica, non-vascular chamber, air flue, sinus, oesophagus, Respiratory cavity, gastrovascular cavity, Stomach duodenum, jejunum and uropoiesis chamber.Gastrovascular cavity include oesophagus, Stomach duodenum, jejunum, small intestine and Large intestine and colon.Preparation includes gas, steam, liquid, solution, emulsion and the suspension of one or more compositions.Make wherein In the case of agent includes the steam of one or more compositions, heat can be generated by the way that steam condensation is turned into liquid in the tissue. Wherein in embodiment of the preparation comprising liquid or solution, cooling or heat can be from being less than or generated more than the formulation temperature of body temperature. The scope of liquid preparation temperature can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -30 DEG C to 80 DEG C.In an embodiment In, the temperature of the tissue through treatment may differ from formulation temperature and below or above body temperature.The temperature range of tissue through treatment It can be 15 DEG C to 100 DEG C, 20 DEG C to 90 DEG C or 36 DEG C to 80 DEG C.In another embodiment, the temperature model of the tissue through treatment Enclosing can be -40 DEG C to -20 DEG C.In some embodiments, delivery catheter is the pin under imaging is oriented to or the conduit based on pin.Into It is one of ultrasound, X-ray, CT scan, MRI, OCT or viewer as being oriented to.Delivery catheter can also be based on air bag or infusion 's.Conduit based on air bag can have single, double or three air bags.Infusion catheter can have dumbbell air bag.Generally, dumbbell infusion air bag In the presence of three parts：Near-end, distal end and middle part.Mid portion has small diameter, and it is with or without infusion hole, and air bag Proximally and distally partly with larger diameter without infusion hole.If the mid portion of dumbbell air bag have hole (Fig. 3 A and 3B) and Distensible infusion methods are defined as, then are transfused from amplifiable conduit portion.Depending on application, the model of initial infusion pressure Enclose can for 0.1atm to 14atm, 1atm to 10atm or 3atm to 8atm.The scope of Infusion Time can be 0.1 minute to 2 small When, 0.5 minute to 30 minutes or 1 minute to 10 minutes.During Infusion Time after initial infusion pressure, the model of gasbag pressure Enclose can for 0.1atm to 3atm, 0.1atm to 2atm and 0.3atm to 1atm.The scope of preparation infusion temperature can be for -40 DEG C extremely 150 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.

In one embodiment, infusion feature can be made up of hypotube (hypotube)/pipe (plastics or metal are made), It is attached to non-porous dumbbell air-sac conduit.When treating preparation and being delivered by hole on hypotube/pipe infusion from it is non-can Conduit portion and hypotube/pipe and air bag are expanded towards wall motion；The infusion is defined as mixing method, it include it is non-it is expansible and The combination of expansible infusion methods.Generally, middle part of the bore portion of hypotube/pipe along dumbbell air bag aligns to control preparation stream Position.

In another embodiment, infusion tube chamber can be placed in catheter shaft, such as non-expansible infusion methods in multitube In chamber axle.In this case, non-expandable part (Fig. 7,8A-8B, 9A-9C) of the hole position between air bag on axle.Device is more specific Example such as double bolloon and three air bag infusion catheters be shown in following sections.

In one embodiment, metal hypotube can have Ahmedabad triangle features (Bard triangle feature), It will strengthen the diffusion of preparation by vascular wall or generating very small hole in the tissue.The altitude range of Ahmedabad triangle can For 0.25-2mm.The infusion methods are mixing methods.

In one embodiment, preparation includes ethanol.Said preparation can as steam or liquid delivery to body cavity tissue. The temperature range of steam or liquid preparation can be -40 DEG C to 150 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.Tissue temperature Scope can be -40 DEG C to 90 DEG C or -30 DEG C to 80 DEG C.In one embodiment, preparation is substantially made up of ethanol.At one In embodiment, preparation is made up of ethanol.

In one embodiment, preparation is the mixture of second alcohol and water.The scope of ethanol content can be 10- by weight 100%.Said preparation can as steam or liquid delivery to body cavity tissue.The temperature range of steam or liquid preparation can be -40 DEG C to 150 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.The temperature range of tissue can be -40 DEG C to 90 DEG C, -30 DEG C to 80 ℃.Ethanol/water preparation can be positive azeotropic mixture.Azeotropic mixture can be 95.63% ethanol and 4.37% water by weight.Ethanol exists 78.4 DEG C of boilings, water seethes with excitement at 100 DEG C and azeotropic mixture is in 78.2 DEG C of boilings, less than its any component.78.2 DEG C be any ethanol/ The minimum temperature that the aqueous solution can seethe with excitement in atmospheric pressure.

In another embodiment, preparation is the steam mixture for including water, ethanol and oxygen.In another embodiment In, preparation is the steam mixture for including water, ethanol and air.In another embodiment, preparation is to include water, ethanol, oxygen The steam mixture of gas and nitrogen.Preparation with oxygen and air is especially effective for treatment asthma and COPD.

In another embodiment, preparation is the steam mixture for including water, ethanol and iodine, including the iodine effectively measured Steam so can in body lumen wall steam mixture be imaged.In another embodiment, preparation be comprising water, ethanol and The liquid mixture of surfactant.In another embodiment, preparation is that the liquid comprising water, ethanol and contrast agent is mixed Thing, including the contrast agent effectively measured so that can by X-ray follow the trail of body lumen wall in mixture.The contrast agent is One of the following：Iodine, ethyl iodide, sodium iodide, lipiodol, nonoxinol iodine, iobitridol, Iohexol, iomeprol, Iopamidol, iodine spray Support, Iopromide, Ioversol, Ioxilan, Iotrolan, Iodixanol, Ioxaglic Acid and its derivative.The content model of contrast agent in preparation It can be 2-20% by weight to enclose, or 5-15% by weight.

In one embodiment, preparation is the mixture of acetic acid and water.The acetic acid content scope of preparation can be for by weight 1-100%, by weight 10-75% or by weight 20-50%.Can be using preparation as steam or liquid delivery to bodily cavity tissue.Steam The temperature range of gas or liquid preparation can be -40 DEG C to 100 DEG C, -30 DEG C to 100 DEG C or -30 DEG C to 80 DEG C.The temperature model of tissue Enclosing can be -30 DEG C to 80 DEG C, 60 DEG C to 80 DEG C or -30 DEG C to -20 DEG C.The temperature range of tissue can be -40 DEG C to 0 DEG C or -30 DEG C to -20 DEG C.Acetic acid content scope in preparation can be for by weight 2% to 75% by weight, or by weight 10% to by weight Amount 60%.

In another embodiment, preparation is that the liquid comprising ethanol and lipiodol (LIPIODOL ULTRA-FLUIDE) is mixed Compound, including the lipiodol effectively measured so that can in body lumen wall steam mixture be imaged and can also damage target god Through tissue.The lipiodol content range of preparation can for by weight 10% to by weight 80%, by weight 15% to by weight 75% or By weight 20% to by weight 50%.In another embodiment, preparation is the liquid mixture comprising water and lipiodol.Preparation Lipiodol content range can be by weight 10% to by weight 80%, by weight 15% to by weight 75% or by weight 20% to by Weight 50%.In another embodiment, preparation is the liquid mixture comprising acetic acid and lipiodol.Lipiodol content model in preparation Enclosing can be by weight 10% to by weight 80%, by weight 15% to by weight 75% or by weight 20% to by weight 50%.

In one embodiment, in the present invention using delivery catheter so that preparation is infused into tissue.Delivering is led Pipe is X-ray or the pin under ultrasonic imaging guiding or the conduit based on pin.Delivery catheter can be based on air bag, its have it is single, double or Three air bags.Delivery catheter can also be based on infusion.Can also be in operation using the combination of air bag and infusion catheter.In infusion system Air bag preparation should be able to be limited in airbag wall and suitably control volumes of formulation.

In one embodiment, in the present invention using expanded balloon conduit for active material to be delivered into patient's body Target position in chamber, the balloon catheter of expansion comprising near-end, distal end, wire, tube chamber, air bag expansion chamber, preparation infusion chamber and/or Vacuum chamber, expansible cell parts and non-expansible axle part, wherein expansible cell parts include at least one portion and not Expansible axle part includes at least one Part I tool of at least one portion, expandable part and/or non-expandable part There are multiple spaces, wherein the space is micropore, and at least one second of expandable part and/or non-expansible axle part Divide and do not have space.The expandable part or non-expandable part of expanded balloon conduit have at least one in the pressure higher than body cavity Power permission preparation penetrates into the space of body lumen wall.Expandable part or non-expandable part do not have in the pressure higher than body cavity Allow the space of air bag expansion body cavity.

As shown in figure 1, delivery catheter 10 has the axle 11 lengthened, it has at least one inner chamber, distal end 13 and near-end 14. It is that near-end 20 and 21 tube chambers of distal end integrate air bag (lumen-conforming balloon) at distal end 13.In any construction In, the pipeline of catheter shaft 11 can be suppressed by plastic material, for example thermoplastic, polyimides, PEI, polyethylene, Polyurethane, polyester, polyamide, Pebax, nylon, fluorinated polyurethane, polyether-ether-ketone, polysulfones etc..Catheter shaft 11 can be with a variety of tube chambers A variety of tube chamber cross sections, including circular or oval tube chamber are suppressed or formed in cross section.In addition, as shown in figure 1, conduit 10 can match somebody with somebody It is ready for use on the distal balloon expansion port 40 of the expansion of distal balloon 21 and the proximal balloon expansion end expanded for proximal balloon 20 Mouth 41, enables near-end 20 and 21 air bags of distal end to separate and expand.The air bag that tube chamber is integrated is can be less than deforming wall of the lumen The air bag expanded under required pressure.Selection is in the flexible and available bag material of high temperature, and then air bag is to comply with when expanded 's.In one embodiment, bag material is one of the following：Polyamide, nylon, Pebax, polyester, polyethylene triphenylmethyl ether or Its copolymer.Depending on the diameter for the treatment of site, air bag diameter may range from about 2 millimeters to about 40 millimeters.In an implementation In scheme, a diameter of about 2 millimeters (" mm ") of each air bag.Alternatively, a diameter of about 3 millimeters of each air bag, or can replace With changing, about 4 millimeters, or alternatively, about 5 millimeters, or alternatively, about 6 millimeters, or alternatively, about 7 millimeters, or can replace With changing, about 8 millimeters, or alternatively, about 9 millimeters, or alternatively, about 10 millimeters, or alternatively, about 12 millimeters, or can Alternatively, about 15 millimeters, or alternatively, about 20 millimeters, or alternatively, about 25 millimeters, or alternatively, about 30 millimeters, Or alternatively, about 35 millimeters, or alternatively, about 40 millimeters.

In one embodiment, at least one slug is located at the near-end and at least one mark of proximal balloon 20 with 22b Remember that band 23a is located at the distal end of distal balloon 21.Balloon catheter can be made up of any appropriate biocompatible material Wire conduit is crossed in fast exchange.Slug band may be additionally located at another end (22a and 23b) of air bag.25 be between air bag 21 and 20 Section, with least one infusion hole.30 be non-expandable part；31 and 32 be microvoid or hole；24 be that cell parts are near The axle at end.40 and 41 namely for the air bag expansion of proximally and distally air bag port.42 be the infusion port of chemicals.

The material of air bag 20 and 21 is made up of one of the following：It is polyester, polyamide, nylon 12, nylon 11, polyamide 12, poly- Block copolymer, Pebax, polyurethane or the polyethers and the block copolymer of polyester of ether and polyamide.The diameter of air bag 21 is equal to Or less than air bag 20.

In one embodiment, the dumbbell air bag of signal is shown in Fig. 2.Under expansion state, its mid diameter D2 is less than Both its end diameter D1 and D3.D1 and D3 can equal or differences in length.Each diameter portion has its own respectively Length L1, L2 and L3.For simple declaration, dumbbell air-sac is used for the description below.However, the air bag of other similar types is such as more Identical feature/function can be achieved in groove air bag (its bracket groove is located in the middle part of air bag).Because two larger ends block formulation flows Path, therefore the design of dumbbell air-sac shape allows air bag that there is more preferable volume infused to control and preparation position in target tube Put control.In one embodiment, the preparation of delivering will be limited in the middle part of small diameter mostly, as shown in Figure 2.For operation Security need controlled therapeutic dose, it means that the larger natural scale between small diameter on dumbbell air bag is by facing Bed administration requirements are determined.To limit the diameter combination on dumbbell air bag, using volume per surface area, and by relative small diameter Volume breach (unappropriated space in small diameter portion) between two larger diameter ends at middle part is calculated.Ratio calculation etc. Formula is：

Volume/surface area=(D1²-D2²)+(4*D1) ... ... equation 1

Wherein D1 is that the diameter and D2 of larger diameter cell parts are the diameters of small diameter cell parts.

The ratio ranges of volume/surface area can be 0.1mm-10mm, 0.2mm-5mm or 0.3mm-2mm.Thus chemical agent Dosage can be constant and independent of air bag or blood vessel size.The value of ratio needs (administration requirements) really by clinical treatment It is fixed.Dumbbell air bag or multiple-grooved air bag can be made up of two grades of heat shrink methods for being related to common cylindrical shaped air bag or directly be molded as Shape.Pneumatophore diameter difference between larger diameter end and intermediate smaller diameter part passes through the advance of volume/surface area ratio It is determined that value determines that it is calculated using equation 1.For example, for the combination of 6mm and 8mm air bags, volume/surface area ratio of calculating To be 0.88mm.

The scope of integral gasbag body diameter and length can be respectively 2-40mm and 10-100mm.The cone angle or shape of conventional balloon Shape is acceptable for application, however, it is preferable that circular or cone.

Any bag material compatible with preparation can be used for manufacture air bag, such as polyethylene, polyolefin elastomer, natural rubber Glue, polyester such as PET and PBT and its block copolymer include thermoplastic elastomer (TPE) such as Hytrel and polyamide such as nylon 12 and nylon 11 and its block copolymer include thermoplastic elastomer (TPE) such as Pebax.

In one embodiment, the schematic diagram of dumbbell air bag infusion catheter is in Fig. 3 A, wherein in intermediate smaller diameter 4 holes in cell parts are separated in 90 degree, and it is changed from Fig. 2, have conical gradual change transition between different-diameter.Liquid Preparation can be delivered from air bag expansion chamber by the hole on air bag；This is a kind of distensible infusion methods.In this example, preparation With both sides role's function：Expanded balloon simultaneously plays a role as therapeutic agent.Fig. 3 B are to expand and position in the blood vessels Infusion balloon catheter schematic diagram.The treatment preparation of most of deliverings is limited in by less pneumatophore and in vascular wall Two larger air bag shoulder generations space.

To strengthen the infusion distance of chemotherapeutant, it can be used air bag outer dia (OD) bigger than internal blood vessel diameter (ID) The ratio expanded in its medium vessels with specific controlled level transition.The scope of ratio can be 1.01 to 10,1.10 to 5 or 1.20 To 1.35.

The micropore on air bag for delivering chemical agent can the life directly on air bag body wall by micro- punching or bore process Into.Appropriate pore diameter range can be 5 microns to 500 microns, or 20 microns to 250 microns on airbag wall.These values are suitably examined Measure the balance of air bag expansion, infusion rate and formulation flows control room.If hole size is excessive, volumes of formulation is due to excess flow It is probably uncontrolled.Geometrically, hole is generally arranged at the center section of small diameter area；However, for delivering preparation Purpose, its on air bag can by different way or pattern place.Hole on air bag can also be in smaller diameter portion centrally along gas All long arrays of bladder walls.The number range in hole can be 2-10 or more and pore diameter range can be 25 microns -100 microns.

Dumbbell air bag in Fig. 3 A can be considered the single slot air capsule with circumferentially 4 holes of mean allocation, air bag above The multiple grooves and each groove that embodiment is additionally included on air bag have the set in the hole for being used to be transfused of its own.For example, three Groove air bag can be made up of the air bag of the length of 80mm length, and infusion agent can be limited in each groove.If its corresponding volume/table Area ratio is equal, and the clinical effectiveness of multiple-grooved air bag can be identical with the conventional barbell air bag shown in Fig. 3 A.Fig. 3 A be used for can Expand the device of infusion methods.

In another embodiment, as shown in figs. 4 a-4b, chemical agent passes through attached with conduit at proximally and distally air bag The tubule delivering connect.In this example, porose dumbbell balloon catheter will not is used for infusion system on air bag.Fig. 4 A-4B are Device for mixing infusing method.Formulation delivered pipe has porous in the cell parts of small diameter.Aperture on pipe Scope can be 25 microns of -1mm.The quantity in hole depends on the length change of small diameter cell parts.Distance range between hole can For 2mm-5mm.

Due to being incorporated with infusion tube in the embodiment shown in Fig. 4 A-4B, air bag expansion and preparation infusion are by dividing The independent operation opened occurs.Such as air bag is expanded to predetermined pressure first, and the chemical agent of subsequent effective volume passes through pipe Treatment site is delivered to, while remaining preparation is limited in the middle part compared with ballonet diameter region.The infusion tube used on conduit Can be by thermoplastic such as polyethylene, nylon or Pebax, or metal or metal alloy such as stainless steel or Nitinol or Nitinol sea Wave duct (due to its super elastic characteristics) is made.

The advantage for exceeding plastic tube using metal or metal alloy pipe is the presence of the feature for additionally serving as formulation delivered.Example Such as, Ahmedabad triangle features may be added to that metal tube (Figure 15).The sharp tip of Ahmedabad triangle can play a role with when air bag is directed to Vascular wall sandwiches tissue wall when expanding.Compared to circular hole version, due to penetrating tissue, therefore the delivery system will allow chemical agent deeper Diffuse into part vascular tissue.If needing deeper diffusion in broader vascular wall area, air bag expansion and deflation number can be made The secondary and rotation after each expansion/deflation cycles.This will cause extra puncturing hole on vascular wall and preparation will be allowed deeper And quickly diffuse through.The altitude range of Ahmedabad triangle can be 0.25mm-2mm or 0.5mm-1mm.

In one embodiment, for treating the asthma and COPD air bag delivery catheter being located in left mainstem bronchus Schematic diagram in Fig. 5 A and 5B.Fig. 5 A and 5B delivery catheter 198 can treat the air flue of the distal end of main bronchus 21 and 22.Example Such as, delivery catheter 198 can be located in lung section influences the remote part of bronchial tree 27 in multiple air flues.Delivery system 198 can be oriented to implement the operation of wide scope, such as a part for such as lobe of the lung, the complete lobe of the lung, multiple lungs by tortuous air flue The denervation of leaf or the lung of one or both sides.In some embodiments, treatment lobar bronchi is with denervation lung Leaf.For example, can target what is be connected along one or more treatment sites of lobar bronchi with denervation with lobar bronchi The complete lobe of the lung.Left lung bronchus can influence upper left leaf and/or lower-left leaf through treating.Right lobar bronchi can be through treating with shadow Ring right upper lobe, right middle lobe and/or right lower lobe.The lobe of the lung can be treated simultaneously or sequentially.In some embodiments, doctor can treat lung Leaf.Validity based on treatment, doctor can simultaneously or sequentially treat other lobes of the lung.By this way, bronchial tree can be treated Different isolated areas.

Delivery catheter 198 can also be used in section or subprovince segmental bronchus.Each section bronchus can be by by preparation It is delivered to along the bronchial single treatment site treatment of section.For example, can be by each section bronchus of formulation delivered to right lung. In certain operations, the application once or twice of preparation can treat most of or complete right lung.Depending on the dissection of bronchial tree Structure, section bronchus can be commonly using once or twice using denervation.

Delivery catheter 198 can influence nerve fiber, while the function or anatomical features of its hetero-organization are maintained, such as muccus gland, Cilium, smooth muscle, body cavity (such as blood vessel).Nerve fiber includes nerve cell, nerve fibre, dendron and supporting tissue such as god Through colloid.Nerve cell transmits electric pulse, and nerve fibre is the aixs cylinder for the extension for performing pulse.Electric pulse is converted into chemistry Signal with effector cell or other nerve cells to communicate.For example, delivery catheter 198 can make the air flue of bronchial tree 27 A part of denervation to weaken the one or more nervous system signals transmitted by nerve fiber.Denervation can be wrapped The nerve fiber for including the neural trunk part of cut-out passes through specific region to the more remote location along bronchial tree to prevent stop signal. If multiple neural trunks extend along air flue, each neural trunk can be cut off.Thus, the nerve along bronchial tree portion can be cut off It is distributed (nerve supply).When signal is cut off, distal end airway smooth muscle relaxation causes Airway dilation.This air flue expands Open and reduce gas-flow resistance, so as to increase the gas exchanges in lung, one or more clinical manifestations are thus mitigated or eliminated, such as exhale Inhale it is difficult, pant, it is uncomfortable in chest etc..Surround or the tissue of neighbouring target nerve tissue may be affected, but not permanent cut-out. In some embodiments, for example, can be to bronchial wall tissue delivery analog quantity along the bronchus blood vessel of the air flue for the treatment of Blood, and along treatment air flue Pulmonary Vascular can before the treatment after delivered in the remote area of bronchial tree 27 to alveolar sac The blood of analog quantity.These blood vessels can continue transport blood to maintain enough gas exchanges.In some embodiments, gas Road smooth muscle will not be injured significantly.For example, not appreciably affecting the relative of smooth muscle in the airway walls of respiratory function Small part can reversibly change.If using preparation in adjusted temperature to damage the nerve fiber outside air flue, the system Agent will not reach the major part of non-targeted smooth muscle tissue.

Fig. 5 A and 5B delivery system 198 include elongated shape in treatment controller 202 and the tube chamber being connected with controller 202 Component 200.Elongated shape component 200 can be inserted into tracheae 20 and utilize or be unfavorable for delivery components and is directed into and by bronchial tree 27.Elongated shape component 200 includes selectively influenceing the distal tip 203 of tissue.

Fig. 5 A controller 202 may include one or more processors, microprocessor, digital signal processor (DSP), existing Field programmable gate array (field programmable gate array, FPGA), application specific integrated circuit (ASIC), storage are set Standby, bus, power supply, pump, preparation source, vapor source, fluid supply, contrast source (contrast resource), steam generator, institute Need temperature preparation generator etc..

Fig. 5 A-5B distal tip 203 can target many places site in lung 10, including but not limited to nerve fiber, fiber Tissue, ill or abnormal structure, musculature, blood, blood vessel and a variety of anatomical features (such as film, body of gland, cilium).

In one embodiment, the schematic diagram of the double bolloon delivery catheter in the arteria renalis is in Fig. 5 C.Fig. 5 C's Balloon catheter 107 can treat hypertension.The arteria renalis wall that preparation is infused to neighbouring renal nerve is used for denervation.Saved in Fig. 5 C Some elements of Renal vascular system are omited.In figure 5 c, 102 be kidney, and 105 be guiding catheter, and 106 be Function failure, and 107 be gas Ductus bursae, 301 be abdominal aorta and 502 be the outer artery of kidney.

In one embodiment, for treat the method for hypertension include by delivery catheter be percutaneously inserted into neighbouring nerve and The outer artery of the arteria renalis and/or kidney of nerve endings；Above-mentioned preparation is infused to adjacent adnerval bodily cavity tissue using delivery catheter, The amount of the preparation wherein delivered can effectively injured nerve and nerve endings, such as example by reducing blood pressure, and finally removed from body cavity Return delivery catheter.

In one embodiment, for example such as Fig. 3 A-3B, 4A-4B, 7,8A-8B and the air bag infusion catheter shown in 9A-9C Available for hypertension therapeutic.The example of preclinical test with embodiment is described below.

In an example, using isoflurane anesthesia body weight 47kg porcine animals, and disappeared using balloon catheter with ethanol Melt the side of its arteria renalis, while the offside arteria renalis plays a role as control.It is using the kidney access operation of standard, air bag is defeated Note conduit is placed in main and additional branches the arteria renalis of kidney of the targeting successively on seal wire.When reaching the ablation site of targeting, Expanded balloon simultaneously enables the arteria renalis chemical ablation of absolute ethyl alcohol mediation to occur via distensible infusion methods.According to kidney blood Pipe radiography determines air bag diameter, and using totally four conduits.During ablation, air bag is set to expand rapidly first by ethanol Until 6-8atm, then slow to be down to 0.5-1atm and kept for about 60 seconds with relatively low pressure.At the end for the treatment of time, make air bag Deflate and recall, or another arterial site is then placed in if necessary to treatment next time.

To obtain more preferable clinical effectiveness, air bag external diameter (OD, larger diameter portion) and Diameter (ID) can be certain Ratio is present.Slightly larger air bag OD can be used than blood vessel ID, such as air bag OD/ blood vessels ID=1.10-1.40；Or=1.20-1.35.

After being melted renal angiography to determine whether there occurs vasopasm, narrow or other exceptions.It is defeated in air bag Note after therapeutic process is neutralized and significant arteria renalis spasm is not present.

By animal euthanasia, and the cranium from cortex renis, middle part and afterbody obtain nephridial tissue sample to use within 2 weeks after treatment Known HPLC methods determine nephridial tissue norepinephrine (NE) content.Norepinephrine is neurotransmitter, and its level is made Canonical measure for kidney denervation plays a role.Also collecting the arteria renalis and surrounding tissue is used for histopathological evaluation.Kidney The Percutaneous ethanol injection ablation of artery causes 72% reduction (the NE contents that renal norepinephrine is reduced：Control：570ng/g；Kidney denervation Dominate, i.e. RDN：160ng/g), as shown in figure 12.

Not only NE contents are reduced after Percutaneous ethanol injection ablation, and histopathological evaluation have also demonstrated renal nerve damage, such as institute in Figure 16 Show, wherein being taken pictures (black arrow) to the nerve that mild fibrosis is surrounded in outer membrane outward flange.

To confirm the result from the studies above, Section 2 research is implemented.Used in confirmation research as above Described identical infusion device and identical study period (2 weeks study for a long period of time).

6 weight 44-56kg porcine animals are divided into three treatment subgroups, wherein two are controlled in Function failure Treat, two are treated in Shen Wai branches, and two are all treated in Function failure and Shen Wai branches.Again, The unilateral treatment of arteria renalis blood vessel is carried out to every animal, while offside is used as control.Implement standard kidney access operation.

Over the course for the treatment of, the air bag OD/ artery ID ratios according to scope in 1.20-1.35 determine air bag size.For More preferable therapeutic effect and minimum injury of blood vessel provide these values by accommodative excess expansion.Rapid expansion is followed in this study The expansion pressure used during ring is 10-12atm；Pressure is then slow to be down to 0.5-1atm, and will be controlled in Function failure site Treatment maintains low pressure 2 minutes and bifurcated artery is maintained 1 minute outside kidney.In all 6 porcine animals in this study, in gas During capsule infusion of therapeutic and afterwards, renal angiography does not show significant arteria renalis spasm.

The renal aorta Percutaneous ethanol injection ablation of only renal aorta causes norepinephrine (NE) averagely to reduce about 40%.Moved outside kidney Arteries and veins branch Percutaneous ethanol injection ablation causes norepinephrine to reduce about 80%.The chemical ablation of Function failure and the outer arterial branch of kidney is common Cause the reduction of the Noradrenaline Contents more than 90%；Cranium cortex norepinephrine is reduced：93.81%th, 94.07%, 94.43%, middle part cortex tissue norepinephrine is reduced：91.98%th, 92.19%, 93.20%, tail cortical tissue removes first kidney Upper parathyrine is reduced：73.27%th, 31.80%, 47.06%.The research confirms the quality of air bag and arteria renalis group in therapeutic process Knit both degree of contact and both contribute to efficient.

Except the reduction in NE, histopathological evaluation confirms renal nerve damage (as shown in Figure 16), and which depict fibre Heavy caliber Perivascular nerve fiber and multifocal degeneration and/or slough that dimensionization and inflammation are surrounded.It has also been observed circumference effect Should.Generally speaking, it is 50% to estimate renal nerve impairment value average in the arteria renalis for the treatment of.

In one embodiment, conduit 10 (in Fig. 1) disclosed herein helps to adjust preparation in entirely treatment window 30 Stream and therapeutic dose, as shown in Figure 6.Air bag can be expanded by its expansion cavity.The position of sidewise hole 31, diameter, number Amount and frequency cause the uniform filling for treating window 30.Fig. 6 describes the conduit in body cavity 5, and it, which has, is located at therapeutic window It is used for two sidewise holes 31 for delivering therapeutic agent 3 in mouth 30.Catheter tip 13, mark band 23a and 23b, expansible air bag 20 and 21 It is shown in Figure 6.As shown in Figure 6, sidewise hole 31 is in fluid communication with inner chamber 25.Sidewise hole 31 in treatment window 30 can be with Exocoel 24 or inner chamber 25 are in fluid communication and then preparation uniform delivery extremely treats window 30.

In one embodiment, as shown in Figure 7, the cross section of the distal portions of three air bag infusion catheters is described Figure.The infusion device can provide uniform filling in treatment site.Air bag in Fig. 7 shows that it is in distal end and closely with expansion state End has two larger-diameter air bag D1 and D3, and has the air bag (D2) of a small diameter at middle part.According to clinical agent Amount needs to use predetermined rate value to pass through the combination of the determination air bag diameter of equation 1.The combination of balloon length depends on target Vasotropic length and curvature.

One of design is the four chamber axles played a role as infusion catheter.Four chambers may specify for wire (1), air bag expansion (1) and chemotherapy (2), for example as shown in fig. 1.Alternatively, conduit can be designed more to be accommodated with more chambers Expansion cavity, wherein each air bag can independently be expanded.

Chemotherapy port is located between the air bag on axle.Preparation infusion hole position is not expansible between expansible cell parts On shaft portion.In therapeutic process, preparation can between air bag by be transfused hole discharge generated with being filled in by small diameter air bag Space in.This is not expansible infusion methods.

In one embodiment, optionally, can be reclaimed after treatment on infusion one of hole by vacuum technique chemical agent/ The residue of preparation.In this case, at least two treatment chambers can be used：One for infusion and another is used for vacuum.System The infusion and vacuum hole of agent are located at the not expansible axle part between expansible cell parts.

Except recalling excessive therapeutic agent, it is possible to use salt solution or water dilute remaining therapeutic agent to non-effective concentration.It can make Implement to rinse with one of conduit line chamber or infusion chamber or by other means with salt solution or water.The method used depend on protection or Treatment site.If the distal portions of blood vessel need the protection from chemotherapy, it can implement to rinse via line chamber.

In one embodiment, as shown in Figure 8 A, new unconventional air bag attachment method can be applied.New method bag Include and air bag waist is placed in air bag cone or air bag main body；This plays a role and surrounds small diameter air bag and by air bag waist to overcome The extra undesired space of the long generation of long and cone, as shown in Figure 7.Additional space does not assign chemotherapy benefit and may Cause over administration due to treatment volume can not be controlled.Preparation be transfused and vacuum hole be located at expansible cell parts between can not Expand on shaft portion.

When additional space is minimized, to confirm the validity of new clothes method of completing the square, similar air bag diameter group is employed Close (Fig. 8 A are than Fig. 7).L (ii) shown in Fig. 8 A is L (i) or L (ii).In expansion state, the tapering of neighbouring air bag is existing will More closely it is in contact with each other, therefore minimizes additional space.Again, preparation delivers between air bag and will fill minor diameter air bag Space on partly/region.

The difference of balloon length is described before and after this new air bag assembly method can be assembled by top.Herein, air bag is long Degree L (i) is defined as the preceding transition point from distal end waist/cone of axle assembling to the length of the transition point of near-end cone/waist；And air bag is long Degree L (ii) is defined as the length from the transition point of distal end waist/cone to the transition point of near-end cone/waist after axle assembling.It is new at this In assembly method, air bag waist is placed in centrum, or in some cases also can be in air bag main body, if centrum length is short Words.Relation between L (i) and L (ii) is：

(1) .L (i)=L (ii)；If air bag is assembled using conventional method.

(2).L(i)>L(ii)；If air bag is assembled using new method.

Depending on the length of air bag centrum, the new infusion catheter will at least 25% in centrum at there is centrum/waist transition Point, or 50 or 100% in centrum at, or partially or completely in air bag main body.

For purposes of illustration, it is considered to be included in distally and proximally all realities of the 8x20mm air bags with 5mm centrum length Example.In this case, L (i)=principal length+distal end cone length+near-end cone length=20+5+5=30mm.Situation 1:Such as Fruit centrum/waist transition point 50% is placed in centrum, then L (ii)=20+2.5+2.5=25mm；L(i)>L(ii).Situation 2:If Centrum/waist transition point 100% is placed in centrum or is placed at the transition wire of centrum/main body, then L (ii)=20+0+0=20mm；L (i)>L (ii), if waist is further arranged in inside, it will be located in air bag main body.

In supravasal multiple air bag component, the air bag with identical L (i) can also have identical or different L (ii).

In another embodiment, conventional taper air bag can be used for the conduit.However, due to its short cone length and phase More surface area contacted potentiality between adjacent cone, it is possible to use circular or conical air bag.

In one embodiment, as shown in Figure 8 B, air bag can be by the way that air bag waist to be placed in or is partially disposed in inversion Air bag waist air bag in be attached on axle.Inverted air bag waist air bag cone can be made more natural mellow and full and will allow cone it Between more contact surface areas；In addition, waist can be more easily placed in pneumatophore.

In one embodiment, when needing narrow treatment band or shorter integral gasbag length, combined using double bolloon.Figure 9A is illustrated in two air bags of the adjacent vertebral in expansion state with contact.Chemical agent can be by the axle between two air bags Delivery port delivering.Preparation is transfused and/or vacuum hole is located on the not expansible axle part between expansible cell parts.Treatment During chemical agent can be retained in the middle part narrow of two air bags.Optionally, extra port can be used for rinsing or vacuum Purpose.Supravasal two air bags can also have the expansion cavity of its own, and therefore can independently expand.

In another embodiment, shown in Fig. 9 B-9C, although integral gasbag length is shorter, can by double diameter air bags For infusion catheter to realize broader treatment length.The air bag has in side with respect to the less two kinds of diameters of opposite side.Adopt Identical mounting technology is arranged with three air bags, double diameter air bags are attached at the axle with the smaller diameter side head to head assembled On to be formed in the middle part of small diameter.Chemical agent mainly is limited in middle part smaller diameter portion to realize by the two ends of diameter portion The delivering of controlled volume.Preparation is transfused and/or vacuum hole is located on the not amplifiable shaft portion between expansible cell parts.Again Secondary, preparation is delivered by the infusion hole on the not expansible axle part between two amplifiable cell parts.

One of double diameter air bags are the taper air bags shown in Fig. 9 B.Double bolloon construction has positioned at head to head right each other Smaller diameter end in the middle part of two air bags in face.The integral diameter of the center section of acquisition is less than end.It is another double straight Footpath air bag is assembled by two benches air bag, as shown in Figure 9 C.There are two kinds of different diameters, i.e. air bag side in an air bag More than opposite side；And two have unexpected diameter change between diameter.Two benches air bag, which can be used, to be faced each other (Fig. 9 C) and is formed Smaller diameter side assembling in the middle part of integral gasbag.Although with the identical integral gasbag length in such as Fig. 9 B, stage air bag can be carried For wider treatment length.

Figure 10 A and 10B illustrate that air bag infusion catheter 365 is located in arteria gastrica 360 or arteria hepatica 320.Around liver and stomach Multiple intra-arterial and innervation liver and stomach and its peripheral organs and a variety of nervous systems of tissue are shown in Figure 10 A and 10B.Liver and Artery around stomach includes abdominal aorta 305, arteria coeliaca 310, arteria hepatica communis 315 and proper hepatic artery 320, gastroduodenal Artery 322, right hepatic artery 325 and left hepatic artery 330, arteria linenalis 335 and esophageal branches 361.Innervation liver and stomach and its week Enclosing a variety of nerves of organ and tissue includes solar plexus 340 and liver neuropile 345.To the blood supply of liver from heart pump Enter sustainer and then pass downwardly through abdominal aorta 305 and enter arteria coeliaca 310.From arteria coeliaca 310, blood is total through liver Artery 315, into proper hepatic artery 320, then enters liver by right side arteria hepatica 325 and left side arteria hepatica 330.Liver always moves Arteries and veins 315 diverges to from coeliac trunk and generates gastroduodenal artery.The nerve of innervation liver includes solar plexus 340 and liver Neuropile 345.Solar plexus 340 winds around arteria coeliaca 310 and goes successively to liver neuropile 345, and it is intrinsic around liver Artery 320 and arteria hepatica communis 315 are wound, and/or are extended on right side arteria hepatica 325 and left side arteria hepatica 330.In some dissections In, solar plexus 340 and the tight adhesion of liver neuropile 345, with blood supply liver, are thus given intravascular to arterial wall To the specific advantage of outer nerve modulation.In several embodiments, the intima-media thickness (such as arteria hepatica) of blood vessel be about 0.1cm extremely About 0.25cm.In some embodiments, can be by formulation delivered to target vessel or the inwall of target nerve.It can be passed using intravascular Send, this is due to nerve and artery outer wall tight adhesion, therefore by blood supply to liver (for example, in the feelings of Branch of hepatic artery In condition).

Artery around stomach includes abdominal aorta 305, arteria coeliaca 310, right arteria gastrica 355 and left arteria gastrica 360 and food Pipe branch 361.Supply, which enters sustainer to the blood of stomach from heart pump and then passes downwardly through abdominal aorta 305 and enter abdominal cavity, to be moved Arteries and veins 310.From arteria coeliaca 310, blood penetrates right arteria gastrica 355 and left arteria gastrica 360, esophageal branches 361 and enters stomach.

With continued reference to Figure 10 A and 10B, liver neuropile 345 is the maximum branch from solar plexus 340.Firmly believe liver god Mainly carried through clump 345 and be transferred into and out sympathetic fiber, its stimulation can increase blood sugar level by number of mechanisms.For example, Stimulating for sympathetic fiber can be by strengthening the generation of hepatic glucose, or by reducing hepatic glucose in liver neuropile 345 Intake increase blood sugar level.Therefore the destruction that sympathetic signal is conducted in liver neuropile 345 can change blood sugar level.

In one embodiment, Figure 10 B are described is used for the air bag delivery catheter for treating diabetes in arteria hepatica Schematic diagram.In another embodiment, Figure 10 A are described is used for the gas for treating obesity and diabetes in left arteria gastrica The schematic diagram of capsule delivery catheter.

Some embodiments of the present invention include steam or liquid preparation being delivered to visceral disc with specific delivery rate Section reaches the predetermined duration.Before delivering, preparation can be heated to at least 80 DEG C, for example, 100 DEG C or 150 DEG C.Conduit material Material, particularly air bag and axle, should be functional in said temperature, because these materials, which are manufactured into, is born high temperature.At some In embodiment, the steam of delivering, which can undergo, mutually fades to liquid, causes energy to discharge, it is passed to tissue.

In some embodiments, for example, safety and effective dosage ranges for treating tissue are about 2cal/g to about 150cal/g, or about 5cal/g to about 100cal/g, and the energy flow rates of delivery system are about 2cal/g to about 500cal/ Second, or about 5cal/ seconds to about 150cal/ seconds.In one embodiment, preparation maker generation steam or liquid preparation, its Middle pressure limit be about 2psi to 200psi and temperature range be about 20 DEG C to 150 DEG C, or about 50 DEG C to 120 DEG C.

The preparation safely effectively measured and/or energy and then satisfactorily injury tissue should be applied.In general, The amount of dosage is related to the degree of injury to tissue.

In some embodiments, the energy range of effective dose is about 1 to about 100cal/g and/or effective preparation agent It is 0.2 microlitre to 200 microlitres to measure scope.These administration limitations can be with other delivery parameter (such as delivery rates or duration Deng) change, in order to be sufficiently accurate it may be desired to different dosage is to realize final optimal damage benefit.

Determine after dosage, should determine that the total amount of the energy (cal) applied via delivery system or preparation (ml).The value passes through The amount (gram) that dosage (cal/g) is multiplied by into tissue to be treated is calculated.

The speed of delivering/flow velocity or delivery system delivering preparation typically determines the duration of preparation.For example, The delivery rate of 30cal/ seconds, by must be 10 seconds the treatment duration to deliver 300 calories.The scope of delivery rate is general It is about 2 to about 200cal/ seconds.Again, these limitation be not it is absolute and may depend on treatment and/or delivery parameter change.

Treatment number of times may depend on the volume of tissue to be treated and the target damage degree of target tissue changed.During treatment Between can be changed to by about 2 seconds about 60 minutes.It is used for induced damage at some with the embodiment of relief of symptoms, it is safe and effective Treatment time scope be about 4 seconds to about 30 minutes.

Delivery rate can be set by adjusting delivery system.Once user determines delivery rate, preparation source will be determined It is expected that the amount of pressure necessary to rate-delivery steam or liquid.Changing delivery rate setting will cause the adjustment of preparation maker to be passed The amount of the pressure sent.Pressure limit in vapor generator can be about 5psi to about 200psi, or about 10psi to about 50psi.

In one embodiment, it is adjacent adnerval including delivery catheter is percutaneously inserted into for treating the method for hypertension The arteria renalis；Using the above-mentioned preparation of catheter infusion and/or heat to adjacent adnerval body cavity tissue, wherein the preparation delivered and/ Or the amount of heat effectively can damage or destroy nerve, such as example by reducing blood pressure；And it is final, recall delivery catheter from body cavity.Heat Purpose be by accelerating preparation and interneural reaction rate to strengthen the effect of damage/destruction.Potential preparation includes one kind Or gas, steam, liquid, solution, emulsion and the suspension of Multiple components.If preparation includes the steaming of one or more compositions Gas, heat can be generated by the way that steam condensation is turned into liquid in the tissue.If preparation includes liquid or solution, heat can be from more than body The high temperature formulations transfer of temperature.The scope of formulation temperature can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.It is adjacent The temperature of the tissue of adnerval treatment can be less than formulation temperature and higher than body temperature.The temperature model of the tissue of adjacent adnerval treatment Enclosing can be -40 DEG C to 100 DEG C, -30 DEG C to 90 DEG C or -20 DEG C to 80 DEG C.The scope of preparation infusion pressure can be for 0.1atm extremely 14atm, 3atm are to 10atm or 4atm to 8atm.

In one embodiment, include delivery catheter inserting adjacent adnerval air flue for treating the method for asthma； Using conduit to be transfused above-mentioned preparation and/or heat to adjacent adnerval airway tissue, wherein the preparation and/or the amount of heat that deliver can Effectively damage or destruction nerve, it is such as example short of breath by alleviating；And it is final, recall delivery catheter from body cavity.The purpose of heat It is by accelerating preparation and interneural reaction rate to strengthen the effect of damage/destruction.Potential preparation includes one or more Gas, steam, liquid, solution, emulsion and the suspension of composition.If preparation includes the steam of one or more compositions, heat can Generated by the way that steam condensation is turned into liquid in the tissue.If preparation includes liquid or solution, heat can be from the height more than body temperature Warm preparation transfer.The temperature range of liquid preparation can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.It is neighbouring The temperature of the tissue of the treatment of nerve can be less than formulation temperature and higher than body temperature.The temperature range of the tissue of adjacent adnerval treatment It can be -40 DEG C to 100 DEG C, -30 DEG C to 90 DEG C or -20 DEG C to 80 DEG C.Preparation infusion pressure scope can for 0.1atm to 14atm, 3atm to 10atm or 4atm to 8atm.

In one embodiment, include delivery catheter inserting adjacent adnerval air flue for treating COPD method； Using conduit to be transfused above-mentioned preparation and/or heat to adjacent adnerval bodily cavity tissue, wherein the preparation and/or the amount of heat that deliver can Effectively damage or destruction nerve, such as example by alleviating COPD symptoms；And it is final, recall delivery catheter from air flue.The purpose of heat It is by accelerating preparation and interneural reaction rate to strengthen the effect of damage/destruction.Potential preparation includes one or more Gas, steam, liquid, solution, emulsion and the suspension of composition.If preparation includes the steam of one or more compositions, heat can Generated by the way that steam condensation is turned into liquid in the tissue.If preparation includes liquid or solution, heat can be from the height more than body temperature Warm preparation transfer.The temperature range of liquid preparation can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.It is neighbouring The temperature of the tissue of the treatment of nerve can be less than formulation temperature and higher than body temperature.The temperature range of the tissue of adjacent adnerval treatment It can be -40 DEG C to 100 DEG C, -30 DEG C to 90 DEG C or -20 DEG C to 80 DEG C.Preparation infusion pressure and/or air bag infusion pressure scope can For 0.1atm to 14atm, 3atm to 10atm or 4atm to 8atm.

In one embodiment, it is adjacent adnerval including delivery catheter is percutaneously inserted into for treating the method for diabetes Arteria hepatica, particularly liver arteria coeliaca, proper hepatic artery and left side and right side arteria hepatica；Using conduit to be transfused above-mentioned preparation And/or heat is to the tissue of adjacent adnerval body cavity, wherein the preparation and/or the amount of heat that deliver effectively can damage or destroy nerve, As for example by reducing glucose level, and finally, delivery catheter is recalled from body cavity.The purpose of heat is by accelerating preparation and god Through reaction rate strengthen damage/destruction effect.Potential preparation includes the gas of one or more compositions, steams air-liquid Body, solution, emulsion and suspension.If preparation includes the steam of one or more compositions, heat can be by the tissue by steam Condensation turns into liquid generation.If preparation includes liquid or solution, heat can be from the high temperature formulations transfer more than body temperature.The temperature of preparation It can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C to spend scope.The temperature of the tissue of adjacent adnerval treatment can Less than formulation temperature and higher than body temperature.The temperature range of the tissue of adjacent adnerval treatment can for -40 DEG C to 100 DEG C, -30 DEG C extremely 90 DEG C or -20 DEG C to 80 DEG C.Preparation infusion pressure and/or air bag infusion pressure scope can for 0.1atm to 14atm, 3atm extremely 10atm or 4atm to 8atm.

In one embodiment, include delivery catheter inserting neighbouring stomach for treating the method for obesity and diabetes With the left and/or right arteria gastrica of nervus esophagi；Using conduit to be transfused above-mentioned preparation and/or heat to adjacent adnerval arteria gastrica group Knit, wherein the preparation and/or the amount of heat that deliver effectively can damage or destroy nerve as example by losing weight；And it is final from stomach Artery recalls delivery catheter.Potential preparation includes gas, steam, liquid, solution, emulsion and the suspension of one or more compositions Liquid.If preparation includes the steam of one or more compositions, heat can be generated by the way that steam condensation is turned into liquid.If preparation bag Liquid or solution are included, heat can be from the high temperature formulations transfer more than body temperature.The temperature range of liquid preparation can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.The temperature of the tissue of adjacent adnerval treatment can be less than formulation temperature and higher than body Temperature.The temperature range of the tissue of adjacent adnerval treatment can be -40 DEG C to 100 DEG C, -30 DEG C to 90 DEG C or -20 DEG C to 80 DEG C.System Agent infusion pressure and/or air bag infusion pressure scope can be 0.1atm to 14atm, 3atm to 10atm or 4atm to 8atm.

In one embodiment, include delivery catheter being percutaneously inserted into neighbour for treating the method for obesity and diabetes Adnerval arteria hepatica, particularly liver arteria coeliaca, proper hepatic artery and left side and right side arteria hepatica；Using conduit to be transfused on Preparation and/or heat are stated to the adnerval hepatic arterial tissue of neighbour；Delivery catheter is recalled from arteria hepatica；Delivery catheter is inserted neighbouring The left and/or right arteria gastrica of stomach and nervus esophagi；Using the above-mentioned preparation of catheter infusion and/or heat to adjacent adnerval arteria gastrica Tissue, wherein the preparation and/or the amount of heat that deliver effectively can damage or destroy nerve, such as example passes through losing weight and glucose Level；And it is final, recall delivery catheter from arteria gastrica.Potential preparation includes the gas of one or more compositions, steams air-liquid Body, solution, emulsion and suspension.If preparation includes the steam of one or more compositions, heat can be by the way that steam condensation be turned into Liquid is generated.If preparation includes liquid or solution, heat can be from the high temperature formulations transfer more than body temperature.The temperature model of liquid preparation Enclosing can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.The temperature of the tissue of adjacent adnerval treatment can be less than Formulation temperature and higher than body temperature.The temperature range of the tissue of adjacent adnerval treatment can be -40 DEG C to 100 DEG C, -30 DEG C to 90 DEG C Or -20 DEG C to 80 DEG C.Preparation infusion pressure and/or air bag infusion pressure scope can be 0.1atm to 14atm, 3atm to 10atm Or 4atm to 8atm.

In one embodiment, include delivery catheter inserting adjacent adnerval digestion for treating the method for obesity Chamber；Using conduit to be transfused above-mentioned preparation and/or heat to the tissue of gastrovascular cavity, wherein the preparation and/or the amount of heat that deliver can have Effect damage or destruction tissue, such as example by losing weight；And finally recall delivery catheter from gastrovascular cavity.For the embodiment Potential gastrovascular cavity include oesophagus, Stomach duodenum, jejunum, small intestine and large intestine and colon.The purpose of heat is by accelerating system Agent and interneural reaction rate strengthen the effect of damage/destruction.Potential preparation includes the gas of one or more compositions, steamed Air-liquid body, solution, emulsion and suspension.If preparation includes the steam of one or more compositions, heat can be by the way that steam be condensed As liquid generation.If preparation includes liquid or solution, heat can be from the high temperature formulations transfer more than body temperature.The temperature of liquid preparation It can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C to spend scope.The temperature of the tissue of adjacent adnerval treatment can Less than formulation temperature and higher than body temperature.The temperature range of the tissue of adjacent adnerval treatment can for -40 DEG C to 100 DEG C, -30 DEG C extremely 90 DEG C or -20 DEG C to 80 DEG C.

In one embodiment, include delivery catheter inserting neighbouring stomach for treating the method for obesity and diabetes With the left and/or right arteria gastrica of nervus esophagi；Using conduit to be transfused above-mentioned preparation and/or heat to adjacent adnerval arteria gastrica group Knit, wherein the preparation and/or the amount of heat that deliver effectively can damage or destroy nerve, such as example by losing weight；And it is final from Arteria gastrica recalls delivery catheter.Potential preparation includes the gas of one or more compositions, steam, liquid, solution, emulsion and outstanding Supernatant liquid.If preparation includes the steam of one or more compositions, heat can be generated by the way that steam condensation is turned into liquid.If preparation Including liquid or solution, heat can be from the high temperature formulations transfer more than body temperature.The temperature range of liquid preparation can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.The temperature of the tissue of adjacent adnerval treatment can be less than formulation temperature and higher than body Temperature.The temperature range of the tissue of adjacent adnerval treatment can be -40 DEG C to 100 DEG C, -30 DEG C to 90 DEG C or -20 DEG C to 80 DEG C.

In one embodiment, for treat obesity and/or diabetes method include by delivery catheter via mouth, Oesophagus and stomach orally insert duodenum and/or jejunum；Using conduit be transfused above-mentioned preparation and/or heat to duodenum and/ Or the surface texture of jejunum reaches 1-30 minutes, wherein the preparation and/or the amount of heat that deliver effectively can damage or destroy surface, body cavity Such as duodenum or the tissue and nerve of jejunum, for example, pass through losing weight and glucose level；Optionally remove or recall system Agent；And finally recall delivery catheter from gastrovascular cavity such as duodenum or jejunum.Potential preparation includes one or more compositions Gas, steam, liquid, solution, emulsion and suspension.If preparation includes the steam of one or more compositions, heat can be by inciting somebody to action Steam condensation turns into liquid generation.If preparation includes liquid or solution, heat can be from the high temperature formulations transfer more than body temperature.Preparation The scope of infusion pressure and/or air bag expansion pressure can be 0.1atm to 14atm, 3atm to 10atm or 4atm to 8atm.Liquid The temperature range of preparation can be -40 DEG C to 140 DEG C, -30 DEG C to 100 DEG C or -20 DEG C to 80 DEG C.The tissue for the treatment of is (in this situation Be surface texture down) temperature can less than preparation temperature and higher than body temperature.The temperature range of the tissue for the treatment of can be for -40 DEG C extremely 100 DEG C, -30 DEG C to 90 DEG C, 36 DEG C to 80 DEG C or 60 DEG C to 80 DEG C.Treatment needs to modify the surface of duodenum or jejunum.Control Treat benefit such as losing weight, glucose level and/or HbA1c (A1C) level and depend on formulation dosage and temperature, the length for the treatment of phase Degree and the duodenal surface area and thickness for the treatment of.In security reason, duodenum perforation is not encouraged.Treat surface modification Duodenal form, nerve and food absorption ability.

In one embodiment, for treating the method for obesity and/or diabetes including non-via mouth, oesophagus and stomach It is invasive that infusion catheter is orally inserted to duodenum and/or jejunum；Using conduit be transfused chemical agent to duodenum and/or The surface texture of jejunum reaches 1-10 minutes, wherein the amount of the chemical agent delivered effectively can damage or destroy the surface of body cavity, tissue And nerve, such as duodenum or jejunum, for example pass through losing weight and glucose level；Optionally remove or recall agent； And finally recall delivery catheter from gastrovascular cavity such as duodenum or jejunum.Chemical agent includes the system of chemical agent and/or absolute ethyl alcohol Agent.It is hereafter the explanation for treating the preclinical test of obesity and/or diabetes.

Whole infusion catheters in the embodiment above can be applied to following researchs.For example, in one is studied, with every The 2-3 grooves dumbbell air-sac in the hole of groove 4 is used for the treatment of obesity and/or diabetes.The scope of air bag diameter and length is respectively 12 to 15 and 55 to 80mm.Implemented to study according to above-mentioned steps.With two childhood Yorkshire hybridized pigs of isoflurane anesthesia (Yorkshire cross pig) (every weighs about 9kg).Balloon catheter will be transfused via mouth, stomach and pylorus in pediatric endoscope Duodenum is downwardly into leading for fluorescope.Ligament of Treitz () is used as to the anatomical landmarks of distal duodenum.Work as delivering When being transfused balloon catheter to duodenum, the quick predilation of air bag is until inject 1.5 to 2.0ml absolute ethyl alcohol after 1.5atm. Then gasbag pressure is maintained at 0.5atm or less than 1-2 minutes.Therapeutic agent serves a dual purpose in this process：(1) air bag Chemicals is delivered to target vessel tissue by expansion and (2) by the hole on airbag wall.After treatment, cell parts bounce back and drawn It is overlapping with next treatment position to avoid to be back to restriction distance.Subsequent repetitive therapy.Bile duct is not treated.2 hours after treatment will Animal euthanasia.Check Duodenal Tissues and suspended 30 minutes in triphenyl tetrazolium chloride (TTC) solution.Chemotherapy Afterwards, slough may show white dot.

The chemical agent used in the studies above is pure acetic acid and absolute ethyl alcohol.From two animals through treatment Be unequivocally established treatment effect in the Duodenal Tissues of TTC dyeing, because white dot is located at the region of chemical ablation.

After above-mentioned short-term research success, implement and study for a long period of time to confirm the clinical benefit for the treatment of.Research include with upper State 7 similar pigs of body weight in short-term research.3 in 7 pigs are handled with absolute ethyl alcohol, 3 use acetic acid, and 1 vacation Processing pig uses salt solution.The same operation before as described in short-term research is used to be used for the treatment of absolute ethyl alcohol.As it is previous Sample, infusion balloon catheter is reached after duodenum, with the rapid predilation air bag of absolute ethyl alcohol until 1.5atm pressure；Then will Ethanol extra about 1.5ml to 2.0ml is injected into duodenum by airbag wall, and then in 0.5atm or following holding pressure 2 minutes.Once treatment phase terminates, the duodenal segment through treatment is then rinsed using endoscope with about 10ml water.

It is similar to be handled with absolute ethyl alcohol with acetic acid treatment and is carried out.As before, treat pig duodenum, specifically with 0.5ml dosage was up to 1 minute.Every time after treatment, cell parts bounce back and are returned to the distance that limits in advance to avoid and next time The overlapping treatment for the treatment of position.Subsequent repetitive therapy.Bile duct is not treated.Recovering animal is used to observe and assess for a long time.

The pig that experience is treated using the duodenum of acetic acid is euthanized for about 5 weeks after the treatment.After clinical and pathology assessment really It is health to determine animal.As demonstrated in Figure 13, using the duodenum treatment of acetic acid compared to false processing animal without significant Weight differences.Glucose level fluctuates and there is no final conclusion.

The pig that experience is treated using the duodenum of absolute ethyl alcohol is euthanized for about 8 weeks after the treatment.Clinical and pathology assessment It is health to determine animal afterwards.As demonstrated in Figure 14, caused using the duodenum treatment of absolute ethyl alcohol compared to false processing animal Less animal weight increase.Glucose there is no final conclusion.

In one embodiment, for treating Barrett esophagus sick (Barrett's esophagus disease) Method includes infusion airbag apparatus, operation and chemical agent.In the method, air bag infusion catheter is passed through under pediatric endoscope guiding Oesophagus is non-invasively inserted by mouth.15mm air bags are generally used in 55 to 80mm scopes length, have at middle part 3 grooves and It is transfused per the micropore of groove 4 for chemical agent.Once air bag is located at target oesophagus, it is until the 1.5atm rapid predilation of pressure is to complete Size.The example of the dosage of delivering is as follows：(1) for the treatment using absolute ethyl alcohol, 1.5ml is passed in the distal portions of oesophagus It is sent to 4 minutes and in proximal part up to 2 minutes；(2) for the treatment using acetic acid, 0.5ml is passed in the distal portions of oesophagus It is sent to 2 minutes and in proximal part up to 1 minute.Once treatment phase terminates, rinsed and controlled using endoscope path way with about 10ml water Treat site.Every time after treatment, portion rebounds air bag is simultaneously moved to other positions for additional procedures.

Using aforesaid operations, implemented and studied for a long period of time with 7 childhood Yorkshire hybridized pigs.Use ethanol treatment 7 3 in pig, 3 are treated using acetic acid, and use brine treatment vacation processing animal.Implement endoscope before and after treatment Check.Recovering animal is used to observe and assess for a long time.Endoscopy also is carried out to animal and entered after 4 weeks within 2 weeks after treatment Go and checked and be euthanized.Therapeutic effect have evaluated by endoscopy.The oesophagus part treated in acetic acid, observed tight The narrow phenomenon of weight.The histopathological analysis for the treatment of part confirms epithelial proliferation and complete epithelium in addition to acetic acid treatment group Change, wherein epithelial layer is not present sometimes.

Above-mentioned preclinical discovery confirms that ethanol treatment is effectively and safe.On the other hand, acetic acid treatment causes through treatment Seriously narrowing and tight beam in oesophagus.In addition, not observing weight compared to untreated animal in the animal that duodenum is treated Measure the difference of change.Known acid corrosion and damage oesophagus inner membrance；Acetic acid produces focus in duodenal wall after topical application.This A bit observation indicate that acetic acid may be unsuitable for duodenum and oesophagus treatment.

In one embodiment, include for treating the method for urologic disease and/or benign prostatic hyperplasis (BPH) Delivery catheter is inserted into uropoiesis chamber；Using conduit be transfused above-mentioned preparation and/or heat to urological tissue such as prostate, urethra and The tube chamber of ureter, wherein the preparation and/or the amount of heat that deliver effectively can damage or destroy tissue, such as example by controlling to urinate Stream；Finally delivery catheter is recalled from uropoiesis chamber.The purpose of heat is damaged by accelerating preparation and interneural reaction rate to strengthen The effect of wound/destruction.Preparation includes gas, steam, liquid, solution, emulsion and the suspension of one or more compositions.If system Agent includes the steam of one or more compositions, and heat can be generated by the way that steam condensation is turned into liquid.If preparation include liquid or Solution, heat can be from the high temperature formulations transfer more than body temperature.The scope of liquid preparation temperature can for -40 DEG C to 140 DEG C, -30 DEG C extremely 100 DEG C or -20 DEG C to 80 DEG C.The temperature of the tissue of adjacent adnerval treatment can be less than formulation temperature and higher than body temperature.Neighbouring god The temperature range of the tissue of the treatment of warp can be -40 DEG C to 100 DEG C, -30 DEG C to 90 DEG C or -20 DEG C to 80 DEG C.Preparation infusion pressure Power and/or the scope of air bag expansion pressure can be 0.1atm to 14atm, 3atm to 10atm or 4atm to 8atm.

In one embodiment, the method for treating cancer or tumour is included under imaging is oriented to by pin or based on pin Conduit is percutaneous or oral insert cancer or tumour；Using conduit to be transfused above-mentioned preparation and/or the hot cancerous tissue to human body, its Cancerous tissue can effectively be damaged, destroy or eliminated to the preparation of middle delivering and/or the amount of heat, such as example by shrinking or eliminating tumour； And finally recall delivery catheter from body.Potential imaging, which is oriented to, to be included ultrasound, X-ray, CT scan, NMR imagings and observes Device.Related cancer include adrenal gland, bladder, cervix, colon, oesophagus, gall-bladder, kidney, liver, lung, ovary, pancreas, prostate, Rectum, stomach and the cancer in uterus.The purpose of heat be by accelerate reaction rate between preparation and cancerous tissue strengthen damage/destruction/ The effect of elimination.Preparation includes gas, steam, liquid, solution, emulsion and the suspension of one or more compositions.If preparation Include the steam of one or more compositions, heat can be generated by the way that steam condensation is turned into liquid in the tissue.If preparation includes Liquid or solution, heat can be from the high temperature formulations transfers more than body temperature.The scope of formulation temperature can be -40 DEG C to 140 DEG C, -30 DEG C To 100 DEG C or -20 DEG C to 80 DEG C.The temperature of the tissue for the treatment of can be less than formulation temperature and higher than body temperature.The temperature of the tissue for the treatment of It can be -40 DEG C to 100 DEG C, -30 DEG C to 90 DEG C or -20 DEG C to 80 DEG C to spend scope.

Claims (38)

1. the method for treating disease, methods described includes：

A) delivery catheter is inserted into body cavity；

B) preparation is transfused to the illing tissue entered in the body cavity, wherein the amount for being delivered to the preparation of the body cavity is effective The illing tissue is damaged or destroys to alleviate disease symptomses；

C) optionally the preparation is removed from the illing tissue；With

D) delivery catheter is recalled from the body cavity.

2. method according to claim 1, wherein the disease is selected from：Hypertension, pulmonary hypertension, diabetes, obesity, the heart Force failure, ESRD, DD, benign prostatic hyperplasis, cancer, tumour, pain, asthma and chronic obstructive pulmonary Sick (COPD).

3. method according to claim 2, wherein cancer are selected from：Adrenal gland, bladder, cervix, colon, oesophagus, gall-bladder, kidney, Liver, lung, ovary, pancreas, prostate, rectum, Stomach duodenum, jejunum and uterine cancer.

4. method according to claim 1, wherein the body cavity is selected from：The arteria renalis, pulmonary artery, lumen of vessels, arteria coeliaca, liver are total It is artery, proper hepatic artery, gastroduodenal artery, right hepatic artery, left hepatic artery, arteria linenalis, right arteria gastrica, left arteria gastrica, non- Lumen of vessels, air flue, sinus, oesophagus, respiratory cavity, gastrovascular cavity, Stomach duodenum, jejunum, prostate, urethra, ureter and/or Uropoiesis chamber.

5. method according to claim 1, wherein the preparation is substantially made up of ethanol.

6. method according to claim 1, wherein the preparation is made up of ethanol.

7. method according to claim 1, wherein the preparation include the gas of one or more compositions, it is steam, liquid, molten Liquid, emulsion or suspension.

8. method according to claim 7, if wherein the preparation includes the steam of one or more compositions, by by described in Steam is condensed into liquid generation heat.

9. method according to claim 7, if wherein the preparation includes liquid or solution, heat is transferred to institute from the preparation State illing tissue.

10. method according to claim 1, if wherein the preparation includes emulsion or suspension, heat is shifted from the preparation To the illing tissue.

11. method according to claim 1, wherein the preparation is in 40 DEG C -140 DEG C of temperature range.

12. method according to claim 1, wherein the preparation is in 0 DEG C -140 DEG C of temperature range.

13. method according to claim 1, wherein the preparation is in -40 DEG C -0 DEG C of temperature range.

14. method according to claim 1, wherein the preparation is in the temperature equal to room temperature.

15. method according to claim 1, wherein the temperature of the illing tissue is less than the temperature of the preparation.

16. method according to claim 1, wherein the temperature of the illing tissue is higher than the temperature of the preparation.

17. method according to claim 1, wherein the pressure limit of the preparation described in infusion process is 0.1atm to 14atm.

18. method according to claim 1, wherein the illing tissue is in -40 DEG C to 100 DEG C of temperature range.

19. method according to claim 1, wherein the illing tissue is in -40 DEG C to 0 DEG C of temperature range.

20. method according to claim 1, wherein the illing tissue is in the temperature equal to body temperature.

21. preparation described in the temperature range in method according to claim 1, wherein infusion process at about -40 DEG C to 150 DEG C Pressure limit is about 2psi-200psi.

22. method according to claim 1, wherein the scope that infusion enters the amount of the preparation of the illing tissue is 0.2 Microlitre to 200 milliliters.

23. method according to claim 1, wherein methods described include the delivery catheter inserting the body cavity about 2 seconds extremely About 60 minutes.

24. method according to claim 1, wherein methods described delivering scope are heat of the about 2cal/g to about 150cal/g amount Or energy is to the illing tissue.

25. method according to claim 1, wherein the delivery catheter is selected from pin or delivery catheter, monosaccate based on pin are passed Send conduit, double bolloon delivery catheter, infusion catheter, air bag infusion catheter, balloon catheter, dumbbell air bag infusion catheter and its group Close.

26. method according to claim 25, wherein the delivery catheter is expanded in 0.1atm-14atm pressure limit.

27. method according to claim 1, wherein the preparation, which is included, is selected from following one or more compositions：Water, salt solution, Hypertonic saline, phenol, methanol, ethanol, absolute alcohol, isopropanol, propyl alcohol, butanol, isobutanol, ethylene glycol, glycerine, acetic acid, breast Acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, iodine Oil, urea and its derivative and combination.

28. method according to claim 1, wherein the preparation, which is included, is selected from following gas or steam：Oxygen, nitrogen, helium It is gas, argon gas, air, carbon dioxide, nitric oxide, water, phenol, methanol, ethanol, absolute alcohol, isopropanol, propyl alcohol, butanol, different Butanol, ethylene glycol, glycerine, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, Isopropyl acetate, ethyl lactate and its mixture.

29. method according to claim 1, wherein the preparation includes the therapeutic agent of the denervation for nerve, wherein The therapeutic agent is selected from：Sodium channel blockers, tetraodotoxin (tetrodotoxin), shellfish poison (saxitoxin), deaminizating Formyl shellfish poison, Vanillin (vanilloid), N-STX (neosaxitoxin), lidocaine, conotoxin (conotoxin), cardiac glycoside (cardiac glycoside), digoxin, glutamic acid, staurosporin (staurosporine), Amlodipine (amlodipine), Verapamil (verapamil), cymarin (cymarin), ocean ground Pornography and drug glycosides (digitoxin), Proscillaridin (proscillaridin), quabain, veratridine (veratridine), cartilage algae Sour (domoic acid), oleandrin (oleandrin), carbamazepine (carbamazepine), aflatoxin (aflatoxin), guanethidine (guanethidine) and guanethidine monosulphate.

30. method according to claim 1, wherein the preparation includes the contrast agent for the denervation for being used to be imaged nerve, Wherein described contrast agent is selected from：Iodine, ethyl iodide, sodium iodide, lipiodol, nonoxinol iodine, iobitridol, Iohexol, iomeprol, iodine Handkerchief alcohol, Iopentol, Iopromide, Ioversol, Ioxilan, Iotrolan, Iodixanol or Ioxaglic Acid, and its derivative.

31. method according to claim 1, wherein the preparation includes azeotropic mixture.

32. according to the method for claim 31, wherein the azeotropic mixture be selected from ethanol/water, propanol/water, isopropanol/water, butanol/ Water, acetic acid/water, lactic acid/water, ethyl lactate/water, ethyl lactate/ethanol, lactic acid/ethanol/water, ethyl lactate/water/ethanol, second Acetoacetic ester/ethanol, ethyl nitrate/ethanol and isopropyl acetate/ethanol.

33. method according to claim 1, wherein the preparation includes ethanol, ethanol/water, ethanol/water/oxygen, ethanol/water/ Air, ethanol/water/contrast agent, ethanol/water/surfactant, ethanol/water/contrast agent/surfactant, propanol/water, isopropyl One of alcohol/water, butanol/water and/or acetic acid/water.

34. for the expanded balloon conduit of the target position by formulation delivered into patient's body lumen, the expanded balloon conduit includes Near-end, distal end, line chamber, air bag expansion chamber, preparation infusion chamber and/or vacuum chamber, expansible air bag and non-expansible axle, wherein institute Stating expansible cell parts and/or non-expansible axle at least includes that there is the Part I in multiple spaces, wherein described space to be Micropore, and wherein described expansible cell parts and/or non-expansible axle at least include the Part II without space.

35. the expanded balloon conduit of claim 34, wherein the expandable part has the first distal end, the first middle part and first Proximal part, wherein the diameter of first distal portions and the first proximal part is more than the diameter of first mid portion.

36. the expanded balloon conduit of claim 34, wherein the expandable part or non-expandable part have at least one The preparation is allowed to enter the space of the wall of the body cavity in the pressure penetration higher than body cavity；And wherein described expandable part or Expandable part, which does not have, allows air bag in the space of the pressure expanded body cavity higher than body cavity.

37. the expanded balloon conduit of claim 34, wherein the body cavity is selected from：The arteria renalis, pulmonary artery, lumen of vessels, abdominal cavity are moved Arteries and veins, arteria hepatica communis and proper hepatic artery, gastroduodenal artery, right hepatic artery, left hepatic artery, arteria linenalis, right arteria gastrica, left stomach Artery, non-vascular chamber, air flue, sinus, oesophagus, respiratory cavity, gastrovascular cavity, Stomach duodenum, jejunum, prostate, urethra, urine output Pipe and uropoiesis chamber.

38. the expanded balloon conduit of claim 34, wherein the preparation is 0.1atm- in scope in delivery process 14atm pressure, and the expansion balloon catheter 0.1atm-14atm pressure limit expand.